The therapeutic role of inhibition of miR-328 on pulmonary carcinoma induced by chlamydia pneumoniae through targeting histone H2AX.

Abstract

Lung cancer represents a major healthy concern due to high incidence and morality. Increasing evidences showed critical regulatory role of microRNA (miR) in cell growth, differentiation and apoptosis. It has been indicated that the level of miR-328 is abnormally up regulated in lung cancer cell line, which is correlated with cell apoptosis. An in vitro lung cancer model was established through induction of chlamydia pneumonia. Western blot and real-time quantitative PCR were used to measure miR-328 level and its effects on histone H2AX expression. Bioinformatics analysis and luciferase reporter gene assay were to determine if H2AX was the direct target of miR-328. TUNEL assay, AV-PI staining and Caspase-3 activity assay measured the effect of the decrease of miR-328 on lung cancer cell apoptosis at both in vivo and in vitro level. Bioinformatics analysis predicted histone H2AX as the target of miR-328 during the regulation of lung cancer. Both in vivo and in vitro knockdown of miR-328 up-regulated H2AX expression and elevated TUNEL-positive cell number. In vivo down-regulation of miR-328 decreased incidence of lung cancer induced by chlamydia pneumoniae, suppressed tumor volume, increased caspase 3 activity, and facilitated tumor cell apoptosis. Histone protein H2AX serves as the target of miR-328 and participates in lung cancer regulation. Suppression of miR-328 level promotes lung cancer tissue apoptosis, which provides novel target for lung cancer therapy.